The present invention relates to controlled release compositions comprised of porous polymeric microbead carriers retaining acne treatment substances within their pores. The invention further relates to methods of preparing such compositions and their methods of use.
Acne is a pleomorphic skin disease characterized by blackheads, whiteheads, papules, pustules, cysts, and various sized nodules and scars which, in the inflammatory stage of the disease, are contaminated with bacteria such as Propionibacterium acnes. The disease involves the pilosebaceous units of the dermis which consist of the sebaceous follicle which include the sebaceous glands and ducts and small hairs.
Sebum (skin oil) is a complex mixture of fats and waxes liberated by the breakdown of the sebaceous cells. The production of sebum is intimately associated with the pathology of acne. Obstruction of the opening of the sebaceous follicle forms a comedo, a solid horny mass or plug made up of keratinized cells and commonly referred to as whiteheads or blackheads, by blocking or stagnating sebum flow through the sebaceous follicle. This blockage may lead secondarily to rupture of the follicular contents (bacteria and sebum) into the dermis, and then to perfolliculitis. This provokes an inflammatory response which leads to the formation of pustules (pimples) when the rupture is small, and cystic nodules with complete rupture. A scar may eventually form, dependent on the depth and extent of the inflammatory response.
Benzoyl peroxide is an oxidizing agent believed to be one of the most effective topical nonprescription medications available for acne. Benzoyl peroxide is one of several topical agents used in treating acne to cause mild irritation and desquamation, thereby preventing closure of the pilosebaceous orifice. The irritant effect of benzoyl peroxide can cause an increased turnover rate of epithelial cells lining the follicular duct, which increases sloughing. The desired effect is to reduce the tendency of the skin to form new comedones and to loosen the structure of the formed comedones and aid in their extrusion. The primary action of benzoyl peroxide, however, is as a bactericide, but it is believed that the irritancy also has a beneficial effect, as described below.
In the past, benzoyl peroxide has been administered to the skin in the form of gels, creams, lotions or ointments in concentrations of 2.5%-5.0% and 10%. There are several disadvantages to prior methods of delivering benzoyl peroxide to affected areas. Strong concentrations of benzoyl peroxide cannot be used because high concentrations of the topical agent can cause localized reactions such as stinging and burning. Benzoyl peroxide is also a strong bleaching agent, and can permanently discolor sheets, pillowcases, towels, clothing or any other colored textiles if a liquid or gel containing the agent is spilled or otherwise contacts such articles.
A common problem with the use of benzoyl peroxide for the treatment of acne has been excessive skin irritation. Although a controlled irritation is believed to contribute to effectiveness, it would be desirable to reduce the side effects of irritancy without substantially reducing the effectiveness of the treatment.